In surgeries of middle otitis including cholesteatoma in the field of otolaryngology, in cases where the mucosa can be preserved, recovery of physiological functions of the mucosa can be expected, and pneumatic space is assured in the middle ear cavity or the mastoid antrum after surgery. However, in many cases of cholesteatoma, it is difficult to preserve the mucosa in the mastoid antrum. Especially, in cases where a large area of the bone surface is exposed, it is highly probable that the formed eardrum is concaved again due to the occlusion of the isthmus of tympanum or due to the postoperative change of the drilled out mastoid antrum to form reconstitutive cholesteatoma (see Non-patent documents 1 and 2). Further, it is known that under such a diseased state, conversion of the mucosa to epithelium after surgery is delayed and the function of gas exchange through the mucosa and the function of the cilia are largely lost.
Accordingly, if the mucosa is regenerated on the surface of the bone exposed in a large area after surgery at an early stage, prevention of the re-adhesion of the eardrum and reconstitutive cholesteatoma is expected. In fact, although transplantation of nasal mucosa or oral mucosa, and use of collagen sponge have been studied, suturing in the narrow middle ear cavity is difficult, and it was found that the exposed bone surface is not appropriate as a scaffold of taking (see Non-patent documents 3 and 4). Further, there are many unclear points about the effect thereof.
Under the background, a novel cell culture method to detach cultured cell without being treated with a protease is described in Patent document 1, wherein cells are cultured at a temperature which below the upper limit or over the lower limit critical dissolution temperature, then the temperature is changed to a temperature which over the upper limit or below the lower limit critical dissolution temperature on the cell culture substrate which covered up its surface with a polymer of which the upper limit or lower limit critical dissolution temperature for water is within a temperature range of 0 to 80° C. Further, an detachment procedure for cultured skin cells with low damage is described in Patent document 2, wherein cells are cultured at a temperature below the upper limit or over the lower limit critical dissolution temperature, then the temperature is changed to a temperature over the upper limit or below the lower limit critical dissolution temperature by using the temperature-responsive cell culture substrate. It has been enabled to plan various new developments for conventional culturing technique by using the temperature-responsive cell culture substrate. As described in Patent document 3, if this technique will be developed more and use real cell existing in a liver tissue for a cell sheet, it is feasible that the sheet could maintain liver tissue cell function for a long term that is impossible by prior art.
However, there has been no discussion about nasal mucosa sheets with specific form.
If a mucosa can be reconstructed promptly on the surface of an exposed bone after the surgery in the operation of a middle otitis, an operative procedure of cholesteatoma of middle ear and adhesive otitis media may be changed. That is, if mucosa of mastoid antrum can be reconstructed after the surgery as expected, the mastoid antrum could be cavernous healing and we expect that plombage of mastoid antrum will be needless. On the other hand, when we think about clinical application to human, some problems surface. Further, there are some problems when a patient has advanced lesion, for example, tissue removal from a middle ear mucosa is difficult and it need preoperation to obtain the mucosa, in some cases, a mucosa from healthy tissue may be needed and ethical problem may also surface. However, nasal mucosa is easy to obtain in outpatient situation and it is preferably less burdens on patients.